ArticleBlood advances2020
Targeting phosphatidylinositol 3 kinase-β and -δ for Bruton tyrosine kinase resistance in diffuse large B-cell lymphoma.
Article in Blood advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 31 citations in OpenAlex.
- DLBCL-microenvironment interactions: cytokine profiling and ECM-mediated ibrutinib resistance in a 3D bone-based model.Medical oncology (Northwood, London, England) · 2026Article
- A network toxicology and molecular docking study predicting putative molecular targets and pathways linking bisphenol a exposure to diffuse large B-cell lymphoma.Discover oncology · 2026Article
- Article
- Mechanisms of chemoresistance in diffuse large B‑cell lymphoma and novel therapeutic strategies (Review).International journal of oncology · 2026Review
- Research Advances on Targets and Mechanisms in Cancers Complicated by Cardiovascular Diseases.OncoTargets and therapy · 2026Review
- Overcoming CAR-T bottlenecks in high-risk DLBCL: a molecular subtyping enhancement strategy.Cancer cell international · 2025Review
- A Bruton tyrosine kinase inhibitor-resistance gene signature predicts prognosis and identifies TRIP13 as a potential therapeutic target in diffuse large B-cell lymphoma.Scientific reports · 2024Article
- Targeting YTHDF2 inhibits tumorigenesis of diffuse large B-cell lymphoma through ACER2-mediated ceramide catabolism.Journal of advanced research · 2024Article
- First-in-class inhibitor of HSP110 blocks BCR activation through SYK phosphorylation in diffuse large B-cell lymphoma.Leukemia · 2024Article
- Safety and efficacy of zandelisib plus zanubrutinib in previously treated follicular and mantle cell lymphomas.British journal of haematology · 2024Article
- Dual PI3K/HDAC Inhibitor BEBT-908 Exhibits Potent Efficacy as Monotherapy for Primary Central Nervous System Lymphoma.Targeted oncology · 2023Article
- Beyond Bruton's tyrosine kinase inhibitors in mantle cell lymphoma: bispecific antibodies, antibody-drug conjugates, CAR T-cells, and novel agents.Journal of hematology & oncology · 2023Review
- Pharmacological Targeting of Bcl-2 Induces Caspase 3-Mediated Cleavage of HDAC6 and Regulates the Autophagy Process in Colorectal Cancer.International journal of molecular sciences · 2023Article
- FOXP1-GINS1 axis promotes DLBCL proliferation and directs doxorubicin resistance.Journal of Cancer · 2023Article
- Resistance to Bruton tyrosine kinase inhibition in chronic lymphocytic leukaemia and non-Hodgkin lymphoma.British journal of haematology · 2023Review
- 5-Hydroxymethylation alterations in cell-free DNA reflect molecular distinctions of diffuse large B cell lymphoma at different primary sites.Clinical epigenetics · 2022Article
- The PI3K/AKT/mTOR signaling pathway is aberrantly activated in primary central nervous system lymphoma and correlated with a poor prognosis.BMC cancer · 2022Article
- Regulation of B-Cell Receptor Signaling and Its Therapeutic Relevance in Aggressive B-Cell Lymphomas.Cancers · 2022Review
- Treatment resistance in diffuse large B-cell lymphoma.Leukemia · 2021Review
- Article
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma; 40% of patients relapse after a complete response or are refractory to therapy. To survive, the activated B-cell (ABC) subtype of DLBCL relies upon B-cell receptor signaling, which can be modulated by the activity of Bruton tyrosine kinase (BTK). Targeting BTK with ibrutinib, an inhibitor, provides a therapeutic approach for this subtype of DLBCL. However, non-Hodgkin lymphoma is often resistant to ibrutinib or acquires resistance soon after exposure. We explored how this resistance develops. We generated 3 isogenic ibrutinib-resistant DLBCL cell lines and investigated the deregulated pathways known to be associated with tumorigenic properties. Reduced levels of BTK and enhanced phosphatidylinositol 3-kinase (PI3K)/AKT signaling were hallmarks of these ibrutinib-resistant cells. Upregulation of PI3K-β expression was demonstrated to drive resistance in ibrutinib-resistant cells, and resistance was reversed by the blocking activity of PI3K-β/δ. Treatment with the selective PI3K-β/δ dual inhibitor KA2237 reduced both tumorigenic properties and survival-based PI3K/AKT/mTOR signaling of these ibrutinib-resistant cells. In addition, combining KA2237 with currently available chemotherapeutic agents synergistically inhibited metabolic growth. This study elucidates the compensatory upregulated PI3K/AKT axis that emerges in ibrutinib-resistant cells.
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